Uveitic glaucoma is a serious, vision-threatening complication of intraocular inflammation and its treatment. Uveitic eyes can develop elevated intraocular pressure (IOP) accompanied by characteristic glaucomatous changes to optic nerve structure and function. 

Pathophysiology

Numerous pathophysiologic mechanisms have been implicated in uveitic glaucoma. Breakdown of the blood-aqueous barrier allows inflammatory cells, serum proteins, and debris to cause trabecular dysfunction and mechanical obstruction.^1,2 In severe, chronic, or recurrent uveitis, trabecular meshwork remodeling increases outflow resistance.^1,3 Pathologic specimens demonstrate thickened trabecular lamellae and increased deposition of extracellular matrix in Schlemm’s canal.³ 

Uveitic glaucoma can also involve secondary angle closure, with posterior synechiae leading to pupillary block and iris bombe; progressive peripheral anterior synechiae; or anterior rotation of the ciliary body.^1,2 Neovascularization and resulting fibrovascular changes can also be seen in the angle.¹

Steroid treatment of intraocular inflammation can contribute to
corticosteroid-induced mechanisms of IOP elevation. Corticosteroid exposure induces deposition of trabecular meshwork extracellular matrix and expression of F-actin, leading to increased stiffness and aqueous outflow resistance.⁴ 

Management

Management of uveitic glaucoma can be clinically challenging. First, there is a high rate of medically refractive uveitic glaucoma.⁵ The relatively younger age at onset of surgical disease implies higher cumulative risk of glaucomatous visual damage during a patient’s lifetime. Additionally, patients with uveitic glaucoma have multiple risk factors for surgical failure, including younger age and inflammation-associated bleb fibrosis. Although antifibrotic agents such as mitomycin-C and 5-fluorouracil have partially offset risks of bleb failure, their use is also associated with increased chronic risks of bleb leak, infection, and hypotony.¹ Currently, glaucoma drainage devices (GDDs) are the preferred surgical intervention in this population, but GDDs are also associated with risk of tube obstruction, bleb encapsulation, tube erosion, infection, or endothelial cell loss.^6-7 

The natural history of uveitic glaucoma poses a significant challenge in the choice of surgical intervention. Patients can experience dramatic IOP spikes, such as in trabeculitis, which are punctuated by periods of normal pressure upon resolution of intraocular inflammation or even hypotony, such as in ciliary body shutdown or increased uveoscleral outflow.² Hypotony following filtering surgery is more common in uveitic glaucoma than in other glaucoma subtypes.^2,7  

Minimally invasive glaucoma surgery (MIGS) is a diverse category of surgical techniques that offers some potential advantages over conventional filtering surgery in uveitic glaucoma. Broadly speaking, MIGS targets the anterior chamber angle and reduces resistance to aqueous drainage at the level of the trabecular meshwork. Although trabeculectomy and GDD establish an alternative aqueous outflow, most MIGS procedures bypass trabecular resistance while preserving function of the conventional outflow tract. 

Minimally Invasive Surgery

There are limited but growing data on the efficacy of goniotomy and gonioscopy-assisted transluminal trabeculotomy (GATT) in uveitic glaucoma management. Initially, goniotomy and other angle surgeries were performed in pediatric patients with juvenile idiopathic arthritis who developed uveitic glaucoma, due to their established efficacy in the pediatric glaucoma population.^8-10 Later, these techniques were adopted in adults with open-angle glaucoma. 

Despite limited peer-reviewed studies of angle surgery in the uveitic glaucoma population, the data appear promising. Goniotomy and GATT both reliably reduce IOP and glaucoma medication burden in uveitic glaucoma eyes.^8-15 In a retrospective case series including 33 eyes with uveitic glaucoma treated with GATT, IOP improved from approximately 31 mmHg on median 4 medications preoperatively to approximately 14 mmHg on median 1 medication at 1 year postoperatively, with only 6% of patients requiring an oral carbonic anhydrase inhibitor.¹¹

The largest available case series reported 24-month surgical outcomes of GATT and goniotomy in uveitic and/or steroid-induced eyes.¹² Of the 40 eyes that underwent GATT, IOP improved from approximately 28 mmHg on mean 3 to 4 medications preoperatively to approximately 13 mmHg on mean 0 to 1 medications at 24 months.¹² Of the 24 eyes that underwent goniotomy, IOP improved from approximately 23 mmHg on 3 to 4 medications preoperatively to approximately 14 mmHg on 1 to 2 medications at 24 months.¹² 

Most patients in these case series required ongoing steroid exposure, suggesting that these angle-based surgeries effectively treated corticosteroid-mediated mechanisms of IOP elevation.^10,12 There were low rates of surgical failure with both groups, as defined by need for additional surgical intervention or loss of light perception vision: GATT 8% and goniotomy 14%.¹² 

Both goniotomy and GATT had favorable safety profiles. Reported intraoperative complications of goniotomy included cyclodialysis cleft, which may require surgical repair if associated with persistent hypotony.¹¹ For GATT, inability to pass the catheter circumferentially may require conversion to an ab externo approach or to goniotomy. Possible causes include obstruction by a valve or stricture within Schlemm’s canal, focal disruption of Schlemm canal by prior glaucoma surgery, or misdirection of the catheter. 

Complications

The most common postoperative complication for both procedures was transient hyphema, which in rare cases required surgical washout (only reported following GATT).^12,15 Transient postoperative IOP elevation or hypotony have also been reported.^10,12 Preoperative assessment should include consideration of temporary cessation of anticoagulant or antiplatelet medications or supplements, if medically acceptable and cleared by the patient’s medical physician, because this may have potential benefits for reducing hyphema risk and/or optimizing intraoperative visibility. 

Potential Advantage of Minimally Invasive Over Traditional Surgery 

Goniotomy and GATT offer several potential advantages over conventional filtering surgeries. Because these techniques are conjunctival-sparing (blebless and sutureless) and do not involve any implant, they avoid complications such as bleb leak, tube erosion, or lifelong infection risk. The patient retains the ability to undergo filtering surgery in the future if indicated. Compared to conventional filtering surgeries, MIGS procedures have lower risk of hypotony due to inherent resistance by episcleral venous pressure. 

Canal-based MIGS also represents a surgical option after prior failed glaucoma surgery. Both goniotomy and GATT have been performed successfully in eyes with prior trabeculectomy or GDD.¹² Goniotomy is more commonly performed in these postsurgical eyes, presumably due to the possibility of focal disruption of Schlemm’s canal that could affect its cannulation.¹² MIGS may be considered as an alternative to a second GDD or cyclophotocoagulation destruction of the ciliary body, which is highly inflammatory. 

Innovation in MIGS instrumentation may advance uveitic glaucoma research by increasing access to tissue specimens. In a proof-of-concept study, trabecular meshwork tissue excised using a Kahook Dual Blade (New World Medical) was adequate for pathologic examination and had higher trabecular meshwork tissue yield compared to traditional pathology samples acquired from ab externo trabeculectomy.¹⁶  

Limitations 

Angle surgery has some limitations. Both goniotomy and GATT are highly reliant on the intraoperative gonioscopic view and may not be feasible in eyes with corneal opacity (such as band keratopathy or edema), extensive peripheral anterior synechiae, or intraoperative bleeding. Traditional GDD insertion may be a better option in these and other potential scenarios, such as in monocular patients for whom postoperative hyphema would significantly affect daily function, patients at high risk of hyphema complications, or medically complex patients who require the highest chance of success from a single operation. Surgical outcomes may also be influenced by individual surgeon experience and skill. 

Bleb-forming Stents

Bleb-forming stents, such as the Xen 45 gel stent (Allergan) or Xen 63 gel stent (the latter is not available in the United States), create an ostomy between the anterior chamber and subconjunctival potential space, resulting in bleb filtration similar to conventional filtering surgery. There is growing literature supporting the efficacy of Xen in uveitic glaucoma.^17-19 Similar complications to conventional filtering surgery have been reported, including hypotony, IOP spikes, implant erosion, need for needling or revision, and endophthalmitis.^17-19 

There are no published studies investigating the safety and efficacy of trabecular bypass stents, such as the Hydrus Microstent (Alcon) and iStent inject W and iStent infinite (Glaukos), in uveitic glaucoma; however, stent occlusion by peripheral anterior synechiae is a risk factor for surgical failure. Additionally, there are case reports of uveitic complications resulting from malposition of the Hydrus Microstent.^20-22 

Conclusion

Canal-based MIGS represents an innovative surgical intervention that targets the site of uveitic glaucoma pathophysiology. There is a strong conceptual foundation and growing empiric evidence to support the role of angle procedures such as goniotomy or GATT as an option for first-line surgical intervention in uveitic glaucoma. GP 

Rebecca Chen, MD, is an assistant professor in the department of ophthalmology and vision science at UC Davis Health in Sacramento, California. Reach her at bcachen@ucdavis.edu.

References

1. Moorthy RS, Mermoud A, Baerveldt G, Minckler DS, Lee PP, Rao NA. Glaucoma associated with uveitis. Surv Ophthalmol. 1997;41(5):361-394. doi:10.1016/s0039-6257(97)00006-4

2. Kalogeropoulos D, Sung VC. Pathogenesis of uveitic glaucoma. J Curr Glaucoma Pract. 2018;12(3):125-138. doi:10.5005/jp-journals-10028-1257

3. Tektas OY, Heinz C, Heiligenhaus A, Hammer CM, Luetjen-Drecoll E. Morphological changes of trabeculectomy specimens in different kinds of uveitic glaucoma. Curr Eye Res. 2011;36(5):442-448. doi:10.3109/02713683.2011.566409

4. Razeghinejad MR, Katz LJ. Steroid-induced iatrogenic glaucoma. Ophthalmic Res. 2012;47(2):66-80. doi:10.1159/000328630

5. Heinz C, Koch JM, Zurek-Imhoff B, Heiligenhaus A. Prevalence of uveitic secondary glaucoma and success of nonsurgical treatment in adults and children in a tertiary referral center. Ocul Immunol Inflamm. 2009;17(4):243-248. doi:10.1080/09273940902913035

6. Vinod K, Gedde SJ, Feuer WJ, et al. Practice preferences for glaucoma surgery: a survey of the American Glaucoma Society. J Glaucoma. 2017;26(8):687-693. doi:10.1097/IJG.0000000000000720

7. Tan AN, Cornelissen MF, Webers CAB, Erckens RJ, Berendschot TTJM, Beckers HJM. Outcomes of severe uveitic glaucoma treated with Baerveldt implant: can blindness be prevented?. Acta Ophthalmol. 2018;96(1):24-30. doi:10.1111/aos.13489

8. Freedman SF, Rodriguez-Rosa RE, Rojas MC, Enyedi LB. Goniotomy for glaucoma secondary to chronic childhood uveitis. Am J Ophthalmol. 2002;133(5):617-621. doi:10.1016/s0002-9394(02)01344-2

9. Sachdev A, Khalili A, Choi J, Stead RE, Sung VCT. Gonioscopy-assisted transluminal trabeculotomy in uveitic glaucoma secondary to juvenile idiopathic arthritis. J Glaucoma. 2020;29(10):e116-e119. doi:10.1097/IJG.0000000000001641

10. Parikh DA, Mellen PL, Kang T, Shalaby WS, Moster MR, Dunn JP. Gonioscopy-assisted transluminal trabeculotomy for the treatment of glaucoma in uveitic eyes. Ocul Immunol Inflamm. 2023;31(8):1608-1614. doi:10.1080/09273948.2022.2087093

11. Belkin A, Chaban YV, Waldner D, et al. Gonioscopy-assisted transluminal trabeculotomy is an effective surgical treatment for uveitic glaucoma. Br J Ophthalmol. 2023;107(5):690-697. doi:10.1136/bjophthalmol-2021-320270

12. Chen RI, Purgert R, Eisengart J. Gonioscopy-assisted transluminal trabeculotomy and goniotomy, with or without concomitant cataract extraction, in steroid-induced and uveitic glaucoma: 24-month outcomes. J Glaucoma. 2023;32(6):501-510. doi:10.1097/IJG.0000000000002183

13. Boese EA, Shah M. Gonioscopy-assisted transluminal trabeculotomy (GATT) is an effective procedure for steroid-induced glaucoma. J Glaucoma. 2019;28(9):803-807. doi:10.1097/IJG.0000000000001317

14. Gunay M, Uzlu D, Akyol N. Outcomes of gonioscopy-assisted transluminal trabeculotomy as a primary surgical treatment for glaucoma secondary to juvenile idiopathic arthritis-associated uveitis. Ocul Immunol Inflamm. 2023;31(10):2060-2064. doi:10.1080/09273948.2023.2221965

15. Miller VJ, Young CEC, SooHoo JR, et al. Efficacy of goniotomy with Kahook Dual Blade in patients with uveitis-associated ocular hypertension. J Glaucoma. 2019;28(8):744-748. doi:10.1097/IJG.0000000000001298

16. Swaminathan SS, Monsalve P, Zhou XY, et al. Histologic analysis of trabecular meshwork obtained from Kahook Dual Blade goniotomy. Am J Ophthalmol. 2018;192:198-205. doi:10.1016/j.ajo.2018.05.028

17. Sng CC, Wang J, Hau S, Htoon HM, Barton K. XEN-45 collagen implant for the treatment of uveitic glaucoma. Clin Exp Ophthalmol. 2018;46(4):339-345. doi:10.1111/ceo.13087

18. Qureshi A, Jones NP, Au L. Urgent management of secondary glaucoma in uveitis using the Xen-45 gel stent. J Glaucoma. 2019;28(12):1061-1066. doi:10.1097/IJG.0000000000001389

19. Serrar Y, Rezkallah A, Kodjikian L, Poli M, Mathis T, Denis P. Xen 63 gel stent to treat a refractory uveitic glaucoma: a case report. Eur J Ophthalmol. 2023;33(4):NP32-NP36. doi:10.1177/11206721221109199

20. Kaplan TM, Sit AJ. A case of uveitis-glaucoma-hyphema syndrome related to a Hydrus Microstent. J Glaucoma. 2024;33(1):51-54. doi:10.1097/IJG.0000000000002287

21. Capitena Young CE, St Peter DM, Ertel MK, Pantcheva MB. Hydrus Microstent malposition with uveitis-glaucoma-hyphema syndrome. Am J Ophthalmol Case Rep. 2022;25:101405. doi:10.1016/j.ajoc.2022.101405

22. Karaca I, Korot E, Ghoraba H, et al. Acute iridocyclitis and cystoid macular edema related to kinked Hydrus^® Microstent in advanced glaucoma. Saudi J Ophthalmol. 2022;36(4):390-393. doi:10.4103/sjopt.sjopt_215_21